Serum albumin concentrations and total body albumin pool sizes are frequently reduced in uremic animals and individuals. Uremic rats have a reduced serum albumin concentration and reduced albumin synthesis in vitro cell free systems despite no differences between their nutritional status and that of control animals. One objective of this proposal is to determine whether albumin synthesis is depressed in vivo in the intact uremic rat compared to pair fed control animals. Tryptophan supplementation prevents the decrease in albumin synthesis caused by CC14 or ethanol intoxication or starvation. A second objective of this proposal is to determine whether dietary tryptophan supplementation prevents the decrease in albumin synthesis seen in uremia in an in vitro cell free system and in vivo. Hepatic intracellular albumin is increased in uremic rats. The additional albumin is found in the cytosol and at least 50% of it is the result of new albumin synthesis. A third objective of this proposal is to determine the mechanism whereby newly synthesize albumin appears in the cytosol and whether this represents a pathologic change in the synthetic and/or secretory pathway for albumin. The nephrotic syndrome is the result of albuminuria and the hypoalbuminemia and hyperlipemia that accompanies this urinary loss. The maximum synthetic capacity of the liver is frequently great enough to make up for the urinary losses but frequently it does not. To determine why this is so. I will measure the rate of albumin synthesis in vivo in nephrotic rats to elucidate the influence of dietary protein and of serum oncotic pressure on the rate of albumin synthesis during the establishment of the nephrotic syndrome.